Nicolas Barbier (PhD student); Céline Monvoisin (engineer); Ansie Martin, PhD (post-doc); Séverine Loisel, PhD (engineer); David Roulois, PhD (CRCN Inserm)
Lymphoid stromal cells (LSC) origin and differentiation process is still a matter of debates. In adult mice, lymph node LSC have been proposed to derive from resident local mesenchymal precursors and to require both TNF and lymphotoxin α1β2 (LT) produced by immune cells for their maturation and maintenance as immunologically competent cells. However, there is still a lack of information regarding the gene regulatory network, transcription factors, and epigenetic cues that control lymphoid stromal cell identity, commitment, and immune properties as well as the mechanism that drive deregulation of these cells in pathological context.
Specific aims adressed in our project
Our project aims at identifying epigenetic drivers of LSC differentiation and deregulation in B-cell lymphomas, in search of putative therapeutic strategies based on stromal cell reprogramming. Using human samples and mouse models analyzed with state-of-the-art epigenetic and transcriptomic profiling, we decided to investigate:
- Kinetics, regulatory networks, and epigenetic mechanisms supporting LSC differentiation, identity, and deregulation in lymphoma
- The role of KDM6B in normal LSC differentiation
- The epigenetic regulation in of immunosuppressive properties of native and clinical-grade mesenchymal stromal cells.